PubMed

Front Microbiol. 2025 Mar 12;16:1553922. doi: 10.3389/fmicb.2025.1553922. eCollection 2025.ABSTRACTINTRODUCTION: Soil microbiome transplantation is a promising technique for enhancing plant holobiont response to abiotic and biotic stresses. However, the rapid assessment of microbiome-plant functional integration in short-term experiments remains a challenge.METHODS: This study investigates the potential of three evergreen sclerophyll species, Pistacia lentiscus (PL), Rosmarinus officinalis (RO), and Juniperus phoenicea (JP), to serve as a reservoir for microbial communities able to confer enhanced tolerance to drought in Salvia officinalis cultivated under water shortage, by analyzing biomass production, plant phenotype, plant ecophysiological responses, and leaf metabolome.RESULTS: Our results showed that the inoculation with the three rhizomicrobiomes did not enhance total plant biomass, while it significantly influenced plant architecture, ecophysiology, and metabolic responses. The inoculation with the JP rhizomicrobiome led to a significant increase in root biomass, resulting in smaller leaves and a higher leaf number. These morphological changes suggest improved water acquisition and thermoregulation strategies. Furthermore, distinct stomatal conductance patterns were observed in plants inoculated with microbiomes from PJ and PL, indicating altered responses to drought stress. The metabolome analysis demonstrated that rhizomicrobiome transplantation significantly influenced the leaf metabolome of S. officinalis. All three rhizomicrobiomes promoted the accumulation of phenolic compounds, terpenoids, and alkaloids, known to play crucial roles in plant defense and stress response. Five molecules (genkwanin, beta-ionone, sumatrol, beta-peltatin-A-methyl ester, and cinnamoyl-beta-D-glucoside) were commonly accumulated in leaves of inoculated sage, independently of the microbiome. Furthermore, unique metabolic alterations were observed depending on the specific inoculated rhizomicrobiome, highlighting the specialized nature of plant-microbe interactions and the possible use of these specific molecules as biomarkers to monitor the recruitment of beneficial microorganisms.DISCUSSION: This study provides compelling evidence that microbiome transplantation can induce phenotypic and metabolic changes in recipient plants, potentially enhancing their resilience to water scarcity. Our findings emphasize the importance of considering multiple factors, including biomass, physiology, and metabolomics, when evaluating the effectiveness of microbiome engineering for improving plant stress tolerance.PMID:40143859 | PMC:PMC11937098 | DOI:10.3389/fmicb.2025.1553922

Front Microbiol. 2025 Mar 12;16:1548427. doi: 10.3389/fmicb.2025.1548427. eCollection 2025.ABSTRACTBACKGROUND: Massa Medicata Fermentata (MMF) is a traditional medicinal/edible fermented product; however, comprehensive research on the fermentation process from a microscopic perspective remains limited. In this study, we aimed to investigate the dynamic changes and correlations of physicochemical properties, microbial communities, and metabolite profiles in different fermentation stages (0, 48, 72, and 96 h) of MMF.METHODS: Standard analytical tests, microbiome sequencing, broad-target metabolism, mixed standard-based mass spectrometry, and fine structure analysis were integrated to elucidate fluctuations in physicochemical, microbial, and metabolic levels during MMF fermentation.RESULTS: During the fermentation process, bacterial diversity generally shows an increasing trend, whereas fungal diversity generally shows a decreasing trend. Revealing that the differentially abundant metabolites were primarily categorized into lipids, amino acids and derivatives, phenolic acids, organic acids, flavonoids, lignans and coumarins, nucleotides and derivatives, and alkaloids. Structural equation modeling and correlation analysis indicated that two species of bacteria (Bacillus velezensis, Bacillus safensis) and four species of fungi (Apiotrichum montevideense, Geotrichum bryndzae, f_Dipodascaceae, Saccharomycopsis fibuligera) showed significant positive correlations with five types of differential metabolites, including lipids, flavonoids, phenolic acids, lignans and coumarins, and organic acids. These differential metabolites are essential components responsible for the therapeutic effects of MMF, particularly those that reach peak concentrations at 72 h of fermentation.CONCLUSION: These findings are expected to provide a reference for developing strategies to strengthen the quality of MMF and promote its modern application.PMID:40143856 | PMC:PMC11936943 | DOI:10.3389/fmicb.2025.1548427

Int J Epidemiol. 2025 Feb 16;54(2):dyaf026. doi: 10.1093/ije/dyaf026.ABSTRACTBACKGROUND: This is the first large-scale longitudinal study of children that describes the temporal trajectories of an extensive collection of metabolic measures that are relevant for lifelong cardiometabolic risk. We also provide a comprehensive picture on how metabolism develops into mature adult sex-specific phenotypes.METHODS: Children born in 1962-92 were recruited by three European studies (n = 20 377 eligible). Biochemical data for ages 0-26 years were available for n = 14 958 participants (n = 8385 with metabolomics). Age associations for 168 metabolic measures (6 physiological traits, 6 clinical biomarkers, and 156 serum metabolomics measures) were determined by using curvilinear regression. Puberty effects were calculated by using logistic regression of biological sex for pre- and post-pubertal age strata.RESULTS: Age-specific concentrations were reported for all measures. Nonlinear age associations were typical, including insulin (R2 = 20.7% ±0.6% variance explained ±SE), glycerol (13.3% ±1.3%), glycoprotein acetyls (40.3% ±1.5%), and branched-chain amino acids (19.5% ±1.6%). Apolipoprotein B was not associated with age (0.7% ±0.4%). Multivariate modeling indicated that boys diverged from girls metabolically during ages 13-17 years. Puberty effects were observed for large high-density lipoprotein cholesterol (P = 8.5 × 10-288), leucine (P < 2.3 × 10-308), glutamine (P < 2.3 × 10-308), albumin (P = 1.7 × 10-161), docosahexaenoic acid (P = 5.2 × 10-50), and sphingomyelin (P = 4.4 × 10-90).CONCLUSION: Novel associations between emerging cardiometabolic risk factors, such as amino acids and glycoprotein acetyls, and growth and puberty were observed. Conversely, apolipoprotein B was stable, which favors its utility for early assessments of lifetime cardiovascular risk.PMID:40143821 | DOI:10.1093/ije/dyaf026

Food Funct. 2025 Mar 27. doi: 10.1039/d4fo06059h. Online ahead of print.ABSTRACTCisplatin (CIS) is a commonly used antitumor drug in clinics, but its application is limited due to hepatotoxicity, nephrotoxicity and gastrointestinal toxicity. In recent years, a large number of studies have shown that the imbalance of intestinal flora is one of the important factors in the malignant development of diseases. Therefore, improving organ function by regulating intestinal flora may be an important strategy to prevent the side effects of chemotherapy drugs. Lycopene (LYC) is found in a wide range of red foods and has antioxidant, anti-inflammatory and immune-enhancing effects. So the purpose of this study was to explore its effect on hepatointestinal injury caused by chemotherapy drugs. The results of this study showed that CIS could significantly restore body weight, diet, water intake, and AST, ALT and other physiological and biochemical indexes of rats. HE staining, projective electron microscopy and TUNEL results showed that LYC alleviated morphological and ultrastructural damage of the liver and intestine. Then, ELISA results showed that LYC can reduce cell apoptosis by increasing the antioxidant capacity and reducing inflammatory response. Secondly, 16sRNA and metabolome results showed that LYC enriched beneficial bacteria (Firmicutes and Proteobacteria), reduced harmful bacteria (E. coli, etc.), enhanced metabolic pathway changes such as taurine and hypotaurine metabolism, and alleviated organ damage caused by CIS. Finally, network pharmacology, molecular docking and immunohistochemistry showed that LYC could reduce CIS induced hepatocyte inflammation and apoptosis by activating the PI3K/AKT pathway. In summary, LYC alleviates the toxic side effects of chemotherapy drugs by regulating the PI3K/AKT pathway and the intestinal microbiota-metabolite-liver axis.PMID:40143795 | DOI:10.1039/d4fo06059h

J Periodontal Res. 2025 Mar 26. doi: 10.1111/jre.13400. Online ahead of print.ABSTRACTAIMS: Poor accuracy of diagnostic and prognostic tools prevents the prediction of peri-implant disease stability or progression. We analyzed metabolites from peri-implant crevicular fluid (PICF) samples from healthy and diseased implants to identify those diagnostic of health and peri-implant disease and predictive of peri-implant bone loss over time.METHODS: Clinical, radiographic examinations and PICF samples were collected from 59 healthy implants, 33 implants with peri-implantitis, and 38 implants with peri-implant mucositis in 71 subjects. A subset of implants was evaluated at 6, 12, 18, and 24 months. Over time, all initially healthy implants remained stable (Group B, N = 28), whereas 6 initially diseased implants continued to lose bone and 8 did not (Group C). PICF metabolites were measured using proton-nuclear magnetic resonance (1H-NMR) 2-dimensional Total Correlation Spectroscopy. PCA and PLS-DA tested the cross-sectional clustering and importance of each metabolite, while the AUC summarized the accuracy of predicting radiographic bone changes ≥ 1 mm at 6-month intervals.RESULTS: At baseline, the Cadaverine/Lysine and Putrescine/Lysine signatures diagnosed peri-implantitis (AUC = 0.76 and 0.70; p < 0.000) with good accuracy, while alpha-ketoglutarate diagnosed implant health (AUC = 0.706; p = 0.002). Combining metabolites increased diagnostic accuracy (AUCCadaverine/Lysine+Methionine = 0.81; p < 0.01). Proline and 1-3-diaminopropane predicted future bone loss (AUCProline = 0.917 and AUC1-3-diaminopropane = 0.854). ANOVA post hoc analysis established that biotin and propionate levels were higher in Group C compared to Groups A and B (p < 0.001; AUCbiotin = 0.889; AUCpropionate = 0.87). Valine levels were higher in Groups A and C compared to Group B (p = 0.002; AUC = 0.841).CONCLUSIONS: 1H-NMR 2-dimensional spectroscopy identified PICF metabolites diagnostic of peri-implantitis with high accuracy. Despite the small number of affected implants, metabolite signatures that predict future bone loss in peri-implantitis appear to be different from those diagnostic of peri-implantitis.PMID:40143571 | DOI:10.1111/jre.13400

Immun Inflamm Dis. 2025 Mar;13(3):e70183. doi: 10.1002/iid3.70183.ABSTRACTOBJECTIVE: Despite growing interest in the gut microbiota and blood metabolome in patients with ankylosing spondylitis (AS), its role remains poorly understood. Here, we investigate how microbial and metabolic alterations contribute to AS.METHODS: Fecal microbiome data from 40 AS patients were compared with those from 40 healthy controls (HCs) using 16S ribosomal RNA (rRNA) gene sequencing. The plasma metabolic profiles were analyzed and integrated with the microbiota data to identify biological characteristics specific to AS.RESULTS: AS patients showed significant enrichment of specific genera, including Megamonas, Elusimicrobium, Dysgonomonas, Ruminococcus_gauvreauii_group, and unclassified_Prevotellaceae. Pathways with the most differentially expressed metabolites included bile secretion; neomycin, kanamycin, and gentamicin biosynthesis; and arachidonic acid metabolism. Positive correlations between Megamonas and Elusimicrobium and metabolites such as piribedil, l-cystathionine, and crocetin dialdehyde suggested microbial enrichment in AS patients.CONCLUSIONS: A disrupted gut microbiota and altered metabolites are present in AS patients. Integrating microbiome and metabolomic data reveals significant disruptions in AS patients, improving our understanding of its pathogenesis.PMID:40143557 | DOI:10.1002/iid3.70183

Pharmaceuticals (Basel). 2025 Mar 12;18(3):398. doi: 10.3390/ph18030398.ABSTRACTBackground and Objectives: Diabetic hepatopathy, characterized by hepatic hypoxia and metabolic dysregulation, has a rising global incidence and prevalence, with limited effective treatments. Hepatic hypoxia activates hypoxia-inducible factor-1 alpha (HIF-1α), regulating sphingolipid metabolism and elevating ceramide, a key factor in insulin resistance. Puerarin (Pue), a flavonoid derived from Pueraria lobata, exhibits therapeutic effects in diabetes, but its effects on hypoxia-related hepatic metabolism are unclear. This study investigates Pue's mechanisms in modulating hepatic metabolism, focusing on HIF-1α and sphingolipid metabolism. Methods: Using bioinformatics and molecular docking, HIF-1α was identified as a key target in diabetic liver disease, confirmed via drug affinity responsive target stability. In vitro experiments utilized insulin-resistant HepG2 cells to assess glucose intake and HIF-1α expression. In vivo, type 2 diabetes mellitus (T2DM) was induced in mice using a high-fat diet and streptozotocin injections. Pue administration was evaluated for its effects on fasting blood glucose, oral glucose tolerance, and hepatoprotective effects. Liver metabolomics and qPCR/Western blot analyses were conducted to assess metabolic pathways. Results: Pue increased glucose uptake in HepG2 cells and bound HIF-1α. Pue reduced HIF-1α expression in HepG2 cells, an effect attenuated by the HIF-1α stabilizer DMOG. Pue improved fasting blood glucose, oral glucose tolerance, and hepatoprotective effects in T2DM mice, which DMOG reversed. Metabolomics revealed that Pue modulates sphingolipid metabolism, decreasing ceramide content. qPCR and Western blot results confirmed that Pue dramatically decreases HIF-1α and SPTLC2 expression. Conclusions: Pue improves diabetic hepatopathy by reducing ceramide expression through the HIF-1α/SPTLC2 pathway, offering a novel therapeutic strategy for diabetes management.PMID:40143173 | DOI:10.3390/ph18030398

Pharmaceuticals (Basel). 2025 Feb 21;18(3):299. doi: 10.3390/ph18030299.ABSTRACTBackground: This is a comparative metabolomic study of the medicinal plant Dryopteris fragrans (L.) Schott from the family Dryopteridaceae Herter (or Aspidiaceae Mett. ex Frank) growing under cold pole conditions in the Oymyakon region of the Republic of Sakha (Yakutia). Methods: The aerial parts of D. fragrans were subjected to extraction using supercritical CO2 extraction and maceration methods. Several experimental conditions were investigated, including a pressure range of 50-300 bar and a temperature range of 31-60 °C. A 1% volume of ethanol was used as a co-solvent in the liquid phase of the extraction. Results: The most effective D. fragrans extraction conditions were 200 Bar pressure and a temperature of 55 °C. Tandem mass spectrometry was used to detect the target analytes. A total of 141 bioactive compounds (86 compounds from the polyphenol group and 55 compounds from other chemical groups) were tentatively identified in extracts of aerial parts of D. fragrans. Among these, thirty chemical constituents from the polyphenol group were identified for the first time. Other compound classes that were newly identified in D. fragrans include naphthoquinones (5,8-dihydroxy-6-methyl-2,3-dihydro-1,4-naphthoquinone, 1,8-dihydroxy-anthraquinone, 1,4,8-trihydroxyanthraquinone, chrysophanol, etc.), diterpenoids (tanshinone IIa, cryptotanshinone, isocryptotanshinone II, tanshinone IIb, etc.), polysaccharides, triterpenoids, and sesquiterpenes. Conclusions: These results highlight that D. fragrans is rich in bioactive compounds and put forward several newly detected compounds for further investigation.PMID:40143079 | DOI:10.3390/ph18030299

J Clin Med. 2025 Mar 17;14(6):2040. doi: 10.3390/jcm14062040.ABSTRACTOncologists increasingly recognize the microbiome as an important facilitator of health as well as a contributor to disease, including, specifically, cancer. Our knowledge of the etiologies, mechanisms, and modulation of microbiome states that ameliorate or promote cancer continues to evolve. The progressive refinement and adoption of "omic" technologies (genomics, transcriptomics, proteomics, and metabolomics) and utilization of advanced computational methods accelerate this evolution. The academic cancer center network, with its immediate access to extensive, multidisciplinary expertise and scientific resources, has the potential to catalyze microbiome research. Here, we review our current understanding of the role of the gut microbiome in cancer prevention, predisposition, and response to therapy. We underscore the promise of operationalizing the academic cancer center network to uncover the structure and function of the gut microbiome; we highlight the unique microbiome-related expert resources available at the City of Hope of Comprehensive Cancer Center as an example of the potential of team science to achieve novel scientific and clinical discovery.PMID:40142848 | DOI:10.3390/jcm14062040

Microorganisms. 2025 Mar 14;13(3):660. doi: 10.3390/microorganisms13030660.ABSTRACTIn this study, we characterized the effects of a diet supplemented with fermented cassava leaves (FCLs) on growth performance, intestinal morphology, the cecal microbiota, and cecal metabolites in hybrid geese. We found that the FCL diet was beneficial to goose growth performance and also promoted a healthy intestinal morphology, as reflected by better morphology properties of the duodenum, jejunum, ileum, and cecum. Moreover, the FCL diet significantly altered cecal microbial diversity and composition, increasing the diversity and abundance of the beneficial Bacteroides. Further, the FCL diet increased the complexity and stability of cecal microbial co-occurrence network interactions as a result of altered topological distributions in the network, such as edges, density, degree, and betweenness. The FCL diet had clear impacts on the composition and abundance of cecal metabolites, with increases in metabolites involved in amino acid biosynthesis, digestion, and absorption, as well as an upregulation of associated metabolic pathways. Based on these benefits to growth performance, intestinal development, and cecal microbe-mediated metabolism in geese, FCLs can be utilized as a reliable feed resource for geese in tropical and subtropical regions.PMID:40142552 | DOI:10.3390/microorganisms13030660

Microorganisms. 2025 Mar 6;13(3):608. doi: 10.3390/microorganisms13030608.ABSTRACTEndosymbiotic bacteria play a significant role in the co-evolution of insects and plants. However, whether they induce or inhibit host plant defense responses remains unclear. In this study, non-targeted metabolomic sequencing was performed on cotton leaves fed with Wolbachia-infected and uninfected spider mites using parthenogenetic backcrossing and antibiotic treatment methods. A total of 55 differential metabolites were identified, which involved lipids, phenylpropanoids, and polyketides. KEGG pathway enrichment analysis revealed seven significantly enriched metabolic pathways. Among them, flavonoid and flavonol biosynthesis, glycerophospholipid metabolism, and ether lipid metabolism showed extremely significant differences. In Wolbachia-infected cotton leaves, the flavonoid biosynthesis pathway was significantly up-regulated, including quercetin and myricetin, suggesting that the plant produces more secondary metabolites to enhance its defense capability. Glycerophosphocholine (GPC) and sn-glycerol-3-phosphoethanolamine (PE) were significantly down-regulated, suggesting that Wolbachia may impair the integrity and function of plant cell membranes. The downregulation of lysine and the upregulation of L-malic acid indicated that Wolbachia infection may shorten the lifespan of spider mites. At various developmental stages of the spider mites, Wolbachia infection increased the expression of detoxification metabolism-related genes, including gene families such as cytochrome P450, glutathione S-transferase, carboxylesterase, and ABC transporters, thereby enhancing the detoxification capability of the host spider mites. This study provides a theoretical basis for further elucidating the mechanisms by which endosymbiotic bacteria induce plant defense responses and expands the theoretical framework of insect-plant co-evolution.PMID:40142501 | DOI:10.3390/microorganisms13030608

Microorganisms. 2025 Mar 4;13(3):587. doi: 10.3390/microorganisms13030587.ABSTRACTFecal microbiota transplantation (FMT) is the most effective therapy for preventing recurrent Clostridioides difficile infection (rCDI). However, the impact of FMT formulations and storage conditions on bacterial viability, community structure, functionality, and clinical efficacy remains under-investigated. We studied the effect of different storage conditions on the bacterial viability (live/dead staining and cell sorting), community structure (16S rDNA analysis), and metabolic functionality (fermentation) of frozen and lyophilized FMT formulations. The clinical success rates of rCDI patients were correlated retrospectively with FMT formulations, storage durations, and host factors using the Edmonton FMT program database. Bacterial viability remained at 10-20% across various storage conditions and formulations and was comparable to that of fresh FMT. Live and dead bacterial fractions in both frozen and lyophilized FMT preparations exhibited distinct community structures. Storage durations, but not temperatures, negatively affected bacterial diversity. More short-chain fatty acids were found in the metabolomic profiling of in vitro fermentation products using lyophilized than frozen FMT. Clinical success rates in 537 rCDI patients receiving a single dose of FMT were not significantly different among the three formulations. However, longer storage durations and advanced recipient age negatively impacted clinical efficacy. Together, our findings suggest that FMT formulations and storage durations should be considered when establishing guidelines for product shelf life for optimal treatment outcomes.PMID:40142480 | DOI:10.3390/microorganisms13030587

Microorganisms. 2025 Feb 22;13(3):492. doi: 10.3390/microorganisms13030492.ABSTRACTFreund's adjuvants have been used in vaccine and autoimmune settings, and their effects can be overlapping or unique to each. While both incomplete Freund's adjuvants (IFA) and complete Freund's adjuvants (CFA) influence antibody and T cell responses, the robust T helper 1 cytokines induced by the mycobacterial components make CFA the powerful immunostimulating adjuvant. In these studies, the adjuvant effects are investigated in a select population of cells, and the changes, if any, with the metabolic alterations in the systemic compartment are unclear. We investigated whether the effects of IFA and CFA can be influenced by the metabolic shifts in mice immunized with saline, IFA, or CFA using Mycobacterium tuberculosis var. bovis Bacillus Calmette-Guérin (BCG) as a positive control. After seven days of immunization, we analyzed the serum metabolite profiles using liquid chromatography coupled with high-resolution mass spectrometry and multivariate statistical analysis to identify metabolic features between the groups. The data revealed that, in the scores space, the CFA and BCG groups were more closely aligned compared to the saline group, while the IFA group displayed an intermediate profile. Furthermore, comparisons between the CFA and BCG groups showed more significant perturbations in lipid and amino acid metabolism, particularly involving glycerophospholipids, cysteine, and aromatic amino acids. In contrast, comparisons between the BCG and IFA groups indicated a more pronounced disruption in central energy metabolism pathways, such as the citric acid cycle and pyruvate metabolism. Together, the data suggest that the serum metabolite profiles in response to IFA and CFA might play a role in modulating the immune responses.PMID:40142385 | DOI:10.3390/microorganisms13030492

Medicina (Kaunas). 2025 Feb 26;61(3):405. doi: 10.3390/medicina61030405.ABSTRACTBackground and Objectives: Liver cancer ranks among the leading causes of cancer-related mortality, necessitating the development of novel diagnostic methods. Deregulated lipid metabolism, a hallmark of hepatocarcinogenesis, offers compelling prospects for biomarker identification. This study aims to employ explainable artificial intelligence (XAI) to identify lipidomic biomarkers for liver cancer and to develop a robust predictive model for early diagnosis. Materials and Methods: This study included 219 patients diagnosed with liver cancer and 219 healthy controls. Serum samples underwent untargeted lipidomic analysis with LC-QTOF-MS. Lipidomic data underwent univariate and multivariate analyses, including fold change (FC), t-tests, PLS-DA, and Elastic Network feature selection, to identify significant biomarker candidate lipids. Machine learning models (AdaBoost, Random Forest, Gradient Boosting) were developed and evaluated utilizing these biomarkers to differentiate liver cancer. The AUC metric was employed to identify the optimal predictive model, whereas SHAP was utilized to achieve interpretability of the model's predictive decisions. Results: Notable alterations in lipid profiles were observed: decreased sphingomyelins (SM d39:2, SM d41:2) and increased fatty acids (FA 14:1, FA 22:2) and phosphatidylcholines (PC 34:1, PC 32:1). AdaBoost exhibited a superior classification performance, achieving an AUC of 0.875. SHAP identified PC 40:4 as the most efficacious lipid for model predictions. The SM d41:2 and SM d36:3 lipids were specifically associated with an increased risk of low-onset cancer and elevated levels of the PC 40:4 lipid. Conclusions: This study demonstrates that untargeted lipidomics, in conjunction with explainable artificial intelligence (XAI) and machine learning, may effectively identify biomarkers for the early detection of liver cancer. The results suggest that alterations in lipid metabolism are crucial to the progression of liver cancer and provide valuable insights for incorporating lipidomics into precision oncology.PMID:40142216 | DOI:10.3390/medicina61030405

Molecules. 2025 Mar 20;30(6):1388. doi: 10.3390/molecules30061388.ABSTRACTUltra-high-performance liquid chromatography coupled to Orbitrap high-resolution mass spectrometry (UHPLC-HRMS) was recently employed in many fields to obtain a rapid characterization of plant extracts. Kigelia africana (family Bignoniaceae) is a quintessential African herbal medicinal plant with immense indigenous medicinal and non-medicinal applications. The aim of the present research was to obtain an in-depth metabolite profiling of the K. africana stem bark extract using UHPLC-HRMS and to conduct a preliminary screening of its anticancer activity against a panel of malignant human cell lines of different origin. The UHPLC-HRMS analysis revealed 63 secondary metabolites including phenolic acids, gallo- and ellagitannins, iridoids, naphthoquinones, and anthraquinones. A total of 34 of all annotated compounds are reported for the first time in K. africana stem bark. The studied profile was dominated by trimethylellagic acid, dimethylellagic acid isomers, and ellagic acid. In all tumor models, we established a pronounced inhibition of cell growth in a mostly dose-dependent manner, with IC50 values ranging near and well below (4-30 µg/mL) the lowest treatment concentration of 25 µg/mL. The established cytotoxicity profile of the K. africana extract, highly biased toward malignantly transformed but not normal cells, suggests specific modulation of defined molecular tumor targets. This study revealed K. africana stem bark as a new source of gallo- and ellagitannins, and highlighted the studied herbal drug as an antiproliferative agent with potential pharmaceutical application.PMID:40142163 | DOI:10.3390/molecules30061388

Molecules. 2025 Mar 14;30(6):1317. doi: 10.3390/molecules30061317.ABSTRACTAssessing the spatial distribution of microorganisms' metabolites in growth medium remains a challenge. Here, we present the first use of the newly developed LARAPPI/CI-MSI 3D (laser ablation remote atmospheric pressure photoionization/chemical ionization mass spectrometry imaging) method for direct three-dimensional (3D) mass spectrometry imaging of bacterial and fungal metabolites in solid culture media. Two-dimensional (2D) MSI was also performed, and it indicated the presence of metabolites belonging to, and including, amino acids and their derivatives, dipeptides, organic acids, fatty acids, sugars and sugar derivatives, benzene derivatives, and indoles. Distribution at a selected depth within the culture medium with the estimation of concentration across all dimensions of 16 metabolites was visualized using LARAPPI/CI-MSI 3D. The imaging results were correlated with the results of ultra-high-performance liquid chromatography-ultra-high-resolution mass spectrometry (UHPLC-UHRMS). A total of 351-393 chemical compounds, depending on the tested microorganism, were identified, while 242-262 were recognized in the HMDB database in MetaboAnalyst (v 6.0). The LARAPPI/CI-MSI 3D method enables the rapid screening of the biotechnological potential of environmental strains, facilitating the discovery of industrially valuable biomolecules.PMID:40142092 | DOI:10.3390/molecules30061317

Molecules. 2025 Mar 8;30(6):1217. doi: 10.3390/molecules30061217.ABSTRACTTocols are commonly known as vitamin E, which comprise tocopherols and tocotrienols. Although vegetable oils are natural sources of tocols, deodorizer distillates (DDs) are attractive feedstock due to their potential abundance from oil refining processes and economic price. Deep eutectic solvents (DESs) are a family of neoteric solvents that show promising performance for tocols extraction. Besides their characters occupying the green chemistry concept, this review presents the current research on the potential performances of DESs in extracting tocols selectively and efficiently from DDs. The application of DESs in tocols extraction is presented considering three different ways: mono-phasic, in situ DESs formation, and bi-phasic systems. The basic principles of intermolecular interactions (H-bond, van der Walls bond, and misfit interaction) between DESs or their components with tocols are discussed to understand the mechanism by which DESs selectively extract tocols from the mixture. This is mainly observed to be a function of the intrinsic properties of DESs and/or tocols, which could be beneficial for tuning the appropriate DESs for extracting tocols selectively and effectively under mild operation conditions. This review is expected to provide insight in the potential application of DESs in the extracting of natural compounds with a phenolic structure and also briefly discusses the toxicity of DESs.PMID:40141994 | DOI:10.3390/molecules30061217

Life (Basel). 2025 Mar 18;15(3):486. doi: 10.3390/life15030486.ABSTRACTPlants experience various abiotic stresses, among which pollutant stress is one of the most damaging, threatening plant productivity and survival. Thiocyanate (SCN-), a recalcitrant byproduct of industrial processes, poses escalating threats to agroecosystems by disrupting plant hormonal homeostasis, which is critical for stress adaptation. Here, we dissect the regulatory interplay of phytohormones in rice (Oryza sativa L.) under SCN- stress (4.80-124.0 mg SCN/L) through integrated transcriptomic and metabolomic profiling. Quantitative hormonal assays revealed dose- and tissue-specific perturbations in phytohormone homeostasis, with shoots exhibiting higher sensitivity than roots. Transcriptomic analysis revealed that a number of differentially expressed genes (DEGs) mapped in different phytohormone pathways in SCN--treated rice seedlings, and their transcript abundances are tissue-specific. To identify the phytohormones governing rice's sensitivity to SCN- stress, we developed a Total Hormonal Sensitivity Index (THSI) through an integrative multivariate framework, which combines Modified Variable Importance in Projection (VIP(m)) scores to quantify hormonal fluctuations and Total Weighted Contribution Scores (TWCS) at the gene-level from hormonal pathways. This study establishes a system-level understanding of how phytohormonal crosstalk mediates rice's adaptation to SCN- stress, providing biomarkers for phytoremediation strategies in contaminated paddies.PMID:40141830 | DOI:10.3390/life15030486

Life (Basel). 2025 Mar 5;15(3):408. doi: 10.3390/life15030408.ABSTRACTPostpartum dairy cows often face significant challenges due to metabolic disorders. Danggui Buxue Tang (DBT), a botanical drug composed of Astragali radix and Angelica sinensis radix in a 5:1 ratio, has been recognized for its potential to alleviate metabolic disorders. Its regulatory mechanisms on livestock metabolic health have remained unexplored. This study integrated the analyses of serum pharmacochemistry, network pharmacology, serum metabolomics, and fecal microbiota to investigate the regulatory effects of DBT on metabolic adaptation in postpartum dairy cows. Following the oral administration of DBT, levels of blood non-esterified fatty acids and beta-hydroxybutyrate were decreased in multiparous dairy cows one week after calving. Five absorbed prototype metabolites of DBT were identified, specifically formononetin and nicotinic acid, both of which play roles in the regulation of lipid metabolic homeostasis. Furthermore, DBT modified the composition of the gut microbial community and glycerophospholipid levels. Decreases in serum phosphatidylethanolamine and phosphatidylcholine levels were closely correlated with the relative abundance of Bacillus and the concentration of circulating beta-hydroxybutyrate. These findings suggest that DBT contributes positively to metabolic health in postpartum dairy cows by regulating the gut microbiota and glycerophospholipid metabolism, providing new insights into strategies for promoting metabolic adaptation in dairy cows.PMID:40141753 | DOI:10.3390/life15030408

Int J Mol Sci. 2025 Mar 20;26(6):2805. doi: 10.3390/ijms26062805.ABSTRACTBacteriophage therapy is a promising approach for targeting antibiotic-resistant bacteria and modulating gut microbiota in metabolic diseases such as obesity. This study evaluated the impact of a two-phage cocktail on an ex vivo colonic simulation model of gut microbiota derived from obese individuals, both in its normalized state and after enrichment with Enterobacter cloacae, an obesity-related bacteria. Microbiological analyses confirmed that the phage cocktail remained active throughout the colonic regions over three digestion cycles and effectively reduced enterobacterial populations in the enriched microbiota. Metabarcoding of the 16S rRNA gene revealed that phage therapy did not significantly alter the abundance of dominant genera, but selectively reduced E. cloacae across all colonic regions. Alpha diversity was significantly affected only in the enriched microbiota, while beta diversity analysis indicated significant compositional shifts during therapy, with reduced dispersion in the final treatment stage. Short-chain fatty acid profiling demonstrated region- and group-specific metabolic responses, with increased lactic and butyric acid concentrations in the ascending colon of the enriched microbiota following phage treatment. This study provides the first ex vivo evidence that a two-phage cocktail can selectively eliminate E. cloacae while preserving overall microbiota structure and functionality. These findings establish a foundation for future in vivo studies exploring the role of phage therapy in reshaping gut microbial communities and metabolic profiles, highlighting its potential as a precision tool for managing gut dysbiosis in metabolic disorders.PMID:40141446 | DOI:10.3390/ijms26062805